Our general
interest is in the area of synthetic organic chemistry, particularly the
development of novel methodologies and their application in the synthesis
of natural products exhibiting unique chemical complexity and significant
biological activity. One of our recent focuses has been
functionalization of olefins with an emphasis on chemo-, regio-, enantio-,
and diastereoselectivity. The following projects highlight some of
our group's recent endeavors (Figure 1).

Figure 1

Epoxidation

Optically active epoxides are
highly versatile synthetic intermediates and present in various natural
products and biologically active molecules.In addition, epoxides have been proposed to be biosynthetic
intermediates for the rapid construction of complex polycyclic natural
products such as brevetoxin B (Figure 2). Asymmetric epoxidation of
olefins provides a powerful approach to the synthesis of such
epoxides.To this end, we have
developed an efficient asymmetric epoxidation method for a variety of trans- and trisubstitued olefins
using fructose-derived ketone 1
as catalyst and Oxone or hydrogen peroxide as oxidants (Figure 3).
Similar results have also been obtained for more electron deficient olefins
using diacetate ketone 2 (Figure
3). Furtherfore, we have found that glucose-derived
ketone 3 can give
high enantioselectivities for the epoxidation of cis- and terminal olefins (Figure 4).
The epoxidation likely proceeds via a chiral dioxirane intermediate
as shown in Figure 5.The asymmetric
epoxidation method has been widely utilized in the synthesis of various
complex molecules and biologically active compounds.

Vicinal diamines are present in many biologically active compounds
(Figure 6). Diamination of olefins presents an attractive strategy
for the selective synthesis of vicinal diamines.We have developed Pd(0)-
and Cu(I)-catalyzed regio- and stereoselective diaminations of olefins
using di-tert-butyldiaziridinone
or its analogues as the nitrogen source (Figure 7).
It is particularly interesting that terminal olefins can be effectively
diaminated at allylic and homoallylic carbons in good yields with high
stereoselectivities via C-H
activation (Figure 8). Furthermore, it has been shown that conjugated
dienes can be regioselectively diaminated at either the terminal or
internal C=C double bond by judicious choice of Cu(I) catalyst (Figure 9).

Cyclopropanes are contained in many biologically and medicinally
important molecules (Figure 10). Moreover, their ring strain allows for
interesting synthetic transformations. The Simmons-Smith reaction is a
widely utilized method for cyclopropantion of olefins.We have
developed a novel class of reagents (RXZnCH2I) that are highly
reactive toward various olefins which had previously been unreactive
(Figures 11 and 12). We further developed a catalytic
asymmetric version of the Simmons-Smith cyclopropanation for
unfunctionalized olefins, which has been a long-standing synthetic
challenge (Figure 13).

In our continuing efforts towards small ring synthesis originating
from carbon-carbon double bonds, we have developed amine catalyzed
aziridinations of electron-deficient olefins to form unprotected aziridines
(Figure 14). Our goals include designing more effective amine
catalysts, development of an asymmetric process, expansion of substrate
scope, and investigation of synthetic applications.